Safe, Effective Dolutegravir Dosing Identified for HIV-Infected Adolescents
SAN DIEGO, CA—Treatment with dolutegravir as part of an optimized background regimen demonstrated good virologic efficacy in adolescents infected with HIV, researchers at IDWeek 2015 reported. In an ongoing Phase 1 and 2 multicenter open-label study (P1093), dolutegravir (DTG) plus optimized background regimen (OBR) proved safe and effective at a dose of about 1mg/kg in adolescents through Week 48, the co-authors reported.
Overall, dolutegravir plus optimized background regimen was “safe and well tolerated in HIV infected adolescents,” reported lead study author Rolando Viani, MD, from the University of California San Diego in La Jolla, CA.
Treatment-experienced children aged ≥12 to <18 years (n=23) with an HIV-1 RNA of ≥1,000 copies/mL (c/mL) were recruited in the study. Study authors measured safety and HIV-1 RNA levels beyond Week 48.
“Virologic success was defined as achieving HIV-1 RNA of <400c/mL based on the FDA snapshot algorithm,” Dr. Viani said. The study's secondary outcome was HIV-1 RNA of <50c/mL at database lock.
Of the study population, median age was 15 years old and median weight was 52.2kg. Median baseline CD4+ cell count was 466 cells/µL and HIV-1 RNA log10 was 4.3 log10c/mL. A total of 19 adolescents were administered dolutegravir 50mg per day and 4 adolescents were administered dolutegravir 35mg per day. The median DTG exposure was 147 weeks (range: 40–194 weeks) and 13 (57%) patients were on the study treatment for ≥144 weeks, Dr. Viani reported.
Virologic success (<400c/mL) was achieved in 39% (9/23; 95% CI: 19.7, 61.5) of patients at Week 144. Also, 30% (7/23; 95% CI: 13.2, 52.9) achieved HIV RNA load <50c/mL at Week 144.
”Invariably, all subjects who experienced virologic failure had incomplete adherence based on 3-day pill recall,” Dr. Viani noted. Ten (43%) of patients discontinued study treatment, “the majority due to noncompliance with the study drug and study visits.”
Of eight study participants for whom drug resistance testing was available at failure, “only one subject had evolution in integrase drug resistance with E138/E/K/T, S147G and R263K at Week 132,” noted Dr. Viani.
Dolutegravir was well tolerated with 5 patients experiencing Grade 3 clinical adverse events and three patients experiencing Grade 3 laboratory abnormalities (none of either category were deemed to be related to the DTG).